chr10-80155890-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_145868.2(ANXA11):c.1481G>A(p.Arg494Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
ANXA11
NM_145868.2 missense
NM_145868.2 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 1.73
Genes affected
ANXA11 (HGNC:535): (annexin A11) This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain calcium-dependent phospholipid-binding sites. The encoded protein is a 56-kD antigen recognized by sera from patients with various autoimmune diseases. Several transcript variants encoding two different isoforms have been identified. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.2629463).
BS2
High AC in GnomAdExome4 at 29 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANXA11 | NM_145868.2 | c.1481G>A | p.Arg494Gln | missense_variant | 16/16 | ENST00000422982.8 | NP_665875.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANXA11 | ENST00000422982.8 | c.1481G>A | p.Arg494Gln | missense_variant | 16/16 | 1 | NM_145868.2 | ENSP00000404412 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251102Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135776
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461860Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17AN XY: 727232
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74348
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Amyotrophic lateral sclerosis Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Dept. of Medical Genetics, Telemark Hospital Trust, Telemark Hospital Trust | Jan 01, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 26, 2020 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ANXA11-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glutamine at codon 494 of the ANXA11 protein (p.Arg494Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
.;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;L
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;D;N
REVEL
Benign
Sift
Benign
D;D;D;D
Sift4G
Uncertain
T;T;T;T
Polyphen
D;D;.;D
Vest4
MutPred
Gain of methylation at K495 (P = 0.0575);Gain of methylation at K495 (P = 0.0575);.;Gain of methylation at K495 (P = 0.0575);
MVP
MPC
0.094
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at